Acute exposure to low-level light at night is sufficient to induce neurological changes and depressive-like behavior

Abstract

The advent and wide-spread adoption of electric lighting over the past century has profoundly affected the circadian organization of physiology and behavior for many individuals in industrialized nations; electric lighting in homes, work environments, and public areas has extended daytime activities into the evening, thus, increasing night-time exposure to light. Although initially assumed to be innocuous, chronic exposure to light at night (LAN) is now associated with increased incidence of cancer, metabolic disorders, and affective problems in humans. However, little is known about potential acute effects of LAN. To determine whether acute exposure to low level LAN alters brain function, adult male and female mice were housed in either light days and dark nights (LD; 14h of 150 lux:10 h of 0 lux) or light days and low level light at night (LAN; 14h of 150 lux:10 h of 5 lux). Mice exposed to LAN on three consecutive nights increased depressive-like responses compared to mice housed in dark nights. Additionally, female mice exposed to LAN increased central tendency in the open field. LAN was associated with reduced hippocampal vascular endothelial growth factor-A (VEGF-A) in both male and female mice, as well as increased VEGFR1 and interleukin-1β mRNA expression in females, and reduced brain derived neurotrophic factor mRNA in males. Further, LAN significantly altered circadian rhythms (activity and temperature) and circadian gene expression in female and male mice respectively. Altogether, this study demonstrates that acute exposure to LAN alters brain physiology and can be detrimental to wellbeing in otherwise healthy individuals.

Circadian rhythm disruption and mental health

“…Although both nocturnal and diurnal species produce melatonin during the dark phase, several common laboratory strains of mice have no detectable pineal melatonin rhythms. Nonetheless, studies using Swiss Webster mice (which have no detectable pineal melatonin) vs. Siberian hamsters (which have a robust pineal melatonin rhythm) have reported similar effects of light at night on affective responses 33,[59][60][61] . This observation suggests that suppressed melatonin by nighttime light is not the only or even primary mechanism, but still may be an important contributor in humans and a potential point of intervention.…”

“…Administration of agomelatine to rats exposed to 3 and 6 weeks of constant light prevented the increase in depressive-like behavior and restored diurnal corticosterone and melatonin rhythms respectively 93,94 . As with constant light, exposure to dim light at night induces depressive-like behavior in multiple species of rodents [58][59][60]95 . In female Siberian hamsters, exposure to 4 weeks of dim light at night (dLAN; 5 lux) increases depressive-like responses and neuroinflammation with concurrent decreases in dendritic spine density within the hippocampus 59 .…”

“…Additionally, diurnal rats exposed to dim light at night (5 lux) for 3 weeks demonstrated increased depressive-like behavior and reduced dendritic length within CA1 and dentate gyrus 58 . Acute (3 nights) exposure of mice to dLAN (5 lux) is sufficient to induce alterations in clock genes and increase depressive-like behavior 60 . However, studies have also reported no association between LAN and mood in C57Bl/6 mice suggesting a potential strain specific effect of LAN 96,97 .…”

“…For example, exposure to dim light at night during early development in mice increases adult anxietylike responses 108,109 , whereas exposure of adult mice to light at night reduces anxiety-like responses 106 . Furthermore, glucocorticoid concentrations are often reduced in hamsters and unaltered in mice exposed to light at night compared to dark nights, suggesting that the affective behavioral responses to atypical lighting are not the result of elevated corticosterone 60,110,111 . Mice housed in 20-h light-dark cycles, a paradigm that disrupts circadian rhythms, display reduced dendritic length and complexity in neurons of the prelimbic prefrontal cortex, associated with anxiety 112 .…”

Photoperiod-Induced Neurotransmitter Switching in the Circadian Pacemaker Regulates Hypothalamic Dopamine Expression

“…Shorter days during winter are associated with seasonal affective disorder and cognitive dysfunction in both humans and nocturnal animals, whereas bright light is an effective therapy for human patients with seasonal or non-seasonal depression 11,13,[79][80][81][82][83][84][85] . Our study showing lightdependent NT plasticity in the SCN-PeVN network is a new mechanism for seasonal adaptation that might prove useful for the development of novel targets and therapeutic approaches for treating seasonal depression and cognitive impairment induced by altered light-dark cycles.…”